The overarching goal of this project is to develop a panel of cardiovascular risk biomarkers that can detect differences in the cardiovascular safety of various tobacco products, whether conventional, new or emerging, in order to help the FDA with the task of regulating them. This will be achieved through 4 aims:

Aim 1: Determine the relative contributions of nicotine and combustion products to the cardiovascular risk of active cigarette smoking.

Will smoke 1 cigarette, NIDA test type with 16.6 mg nicotine; 1 cigarette, NIDA test type with <0.45 mg nicotine; perform sham smoking by puffing on a drinking straw. Each intervention will last 10 minutes, and each will take place one time, on one of 3 study visits, in random order.

Other: Cigarette, NIDA test type with 16.6 mg nicotine

Smoke a single cigarette for up to 10 minutes

Other Name: Cigarette

Other: Cigarette, NIDA test type with <0.45 mg nicotine

Smoke a single low-nicotine cigarette for up to 10 minutes

Other Name: Cigarette

Other: sham smoking

Sham smoking or e-cigarette use consists of puffing on a drinking straw for 10 minutes

Experimental: Nonsmokers

Will undergo secondhand cigarette smoke (SHS) exposure and conditioned, filtered air exposure. Each intervention will last 180 minutes, and each will take place one time, on one of 2 study visits, in random order.

Other: Secondhand cigarette smoke (SHS)

180-minute exposure to SHS generated by controlled dilution of smoke from machine-smoked cigarettes

Other Names:

environmental tobacco smoke

ETS

SHS

Other: Conditioned, filtered air

Exposure to conditioned, filtered air for 180 minutes

Other Names:

Clean, filtered, temperature and humidity controlled air

Negative control for SHS exposure

Experimental: Smokeless tobacco users

Will use 1 pouch of commercially available moist oral snuff and will chew gum (sham moist snuff). Each intervention will last 30 minutes, and each will take place one time, on one of 2 study visits, in random order.

Other: Moist snuff

Use moist snuff for 30 minutes

Other Name: commercially available moist oral snuff

Other: sham moist snuff

Chew gum for 30 minutes

Other Names:

Chewing gum

Negative control for moist oral snuff use

Experimental: e-cigarette users

Will use one electronic cigarette with 18 mg/ml nicotine, one electronic cigarette with no nicotine, and will perform sham smoking by puffing on a drinking straw. Each intervention will last 10 minutes, and each will take place one time, on one of 3 study visits, in random order.

Other: Electronic cigarette with 18 mg/ml nicotine

Use electronic cigarette with 18 mg/ml nicotine for 30 minutes

Other: Electronic Cigarette with no nicotine

Use electronic cigarette with no nicotine for 30 minutes

Other: sham smoking

Sham smoking or e-cigarette use consists of puffing on a drinking straw for 10 minutes

Detailed Description:

Cigarette smoking is a major cause of cardiovascular disease (CVD).1 In contrast, the cardiovascular risks of other popular tobacco products (smokeless tobacco), new tobacco products ( e-cigarettes) and proposed products (reduced nicotine cigarettes) are not adequately understood. The FDA will need information about the cardiovascular safety of these products to inform their regulatory decisions. While long-term clinical outcome studies of the cardiovascular risks of these tobacco products would be optimal, they take too long to provide the data that the FDA needs now. Disturbances in the function of vascular endothelium (the lining of arteries, which plays an important role in regulating vascular function) and the activation of the autonomic nervous system, as well as increased inflammation, oxidative stress and propensity to thrombosis (clotting), are key mechanisms in the progression of CVD and validated biomarkers of CVD risk. These biomarkers form the basis for our model to assess the CVD risks of tobacco product use and secondhand smoke exposure. We will conduct controlled, short-term exposures of human subjects to test products that provide a wide range of nicotine, particle, and other cardiovascular toxin concentrations to determine how these components associated with tobacco use adversely affect cardiovascular risk.

Eligibility

Ages Eligible for Study:

18 Years to 50 Years (Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

All Groups: Age 18-50

Can tolerate withholding their medications for two weeks at a time

Group 1: Active smokers

Group 2: Nonsmokers

Group 3: Active users of smokeless tobacco

Group 4: Active users of electronic cigarettes

Additional Inclusion Criteria for E-Cigarette Users:

Currently use ofe-cigarettes > 5 times a day

Has used e-cigarettes for >3 months

Additional Inclusion Criteria for Active Smokers: Currently smoke >5 cigarettes per day ≥ 1 pack year

Exclusion Criteria:

Exclusion Criteria for all subjects

Physician diagnosis of:

asthma

heart disease

hypertension

dyslipidemia

thyroid disease

diabetes

renal or liver impairment

glaucoma.

Unstable psychiatric condition (such as current major depression, history of schizophrenia or bipolar disorder)

current use of more than two psychiatric medications

Pregnancy or breastfeeding (by history)

Alcohol, opiate, cocaine, amphetamine or methamphetamine dependence within the past 5 years

BMI > 35 and < 18

Current opiate, cocaine, amphetamine or methamphetamine use (by history or urine test)

Occupational exposure to smoke, dusts and fumes

Concurrent participation in another clinical trial

Unable to communicate in English

Additional Exclusion Criteria for Active Smokers:

Unable to hold marijuana for 1 week prior to each study visit.

Exhaled CO <10 ppm at each visit

Negative salivary cotinine test using a rapid-read, over the counter test with 30 ng/ml cutoff

Additional Exclusion Criteria for Nonsmokers:

More than 1 pack year smoking history

Quit smoking < 5 years ago

Ever a daily marijuana smoker

Smoked anything within the last 3 months

Additional Inclusion Criteria for Smokeless Tobacco Users:

Use of moist oral snuff > 5 times a day

Has used moist oral snuff for at least 0.5 years

Additional Exclusion Criteria for Smokeless Tobacco Users:

Current smoker

Quit smoking < 0.5 years ago

Additional Exclusion Criteria for E-Cigarette Users:

Current use of other tobacco products

Unable to hold marijuana for 1 week prior to each study visit

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01964807